6-31542328-A-G

Variant names:

• chr6-31542328-A-G
• rs2239528
• ENST00000458640.5:c.-381T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000458640.5(DDX39B):​c.-381T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 683,760 control chromosomes in the GnomAD database, including 195,635 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.76 (44694 hom., cov: 33)
  • Exomes 𝑓: 0.75 (150941 hom.)
• Consequence: DDX39B ENST00000458640.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.464
• Publications: 40 publications found

Genes affected

DDX39B (HGNC:13917): (DExD-box helicase 39B) This gene encodes a member of the DEAD box family of RNA-dependent ATPases that mediate ATP hydrolysis during pre-mRNA splicing. The encoded protein is an essential splicing factor required for association of U2 small nuclear ribonucleoprotein with pre-mRNA, and it also plays an important role in mRNA export from the nucleus to the cytoplasm. This gene belongs to a cluster of genes localized in the vicinity of the genes encoding tumor necrosis factor alpha and tumor necrosis factor beta. These genes are all within the human major histocompatibility complex class III region. Mutations in this gene may be associated with rheumatoid arthritis. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on both chromosomes 6 and 11. Read-through transcription also occurs between this gene and the upstream ATP6V1G2 (ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2) gene. [provided by RefSeq, Feb 2011]

ATP6V1G2-DDX39B (HGNC:41999): (ATP6V1G2-DDX39B readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring ATP6V1G2 (ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2) and DDX39B (DEAD box polypeptide 39B) genes located in the major histocompatibility complex class III region of chromosome 6. The read-through transcript and is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

DDX39B-AS1 (HGNC:39771): (DDX39B antisense RNA 1)

ENSG00000299760 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX39B-AS1	NR_133674.1	n.25A>G		non_coding_transcript_exon_variant	Exon 1 of 2
DDX39B-AS1	NR_133675.1	n.25A>G		non_coding_transcript_exon_variant	Exon 1 of 2
ATP6V1G2-DDX39B	NR_037853.1	n.473-180T>C		intron_variant	Intron 2 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V1G2-DDX39B	ENST00000376185.5	n.184-180T>C		intron_variant	Intron 2 of 12	2		ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.763 AC: 116027 AN: 152002 Hom.: 44647 Cov.: 33

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.788

GnomAD2 exomes AF: 0.773 AC: 105858 AN: 136984 AF XY: 0.771

Gnomad AFR exome AF: 0.826

Gnomad AMR exome AF: 0.816

Gnomad ASJ exome AF: 0.852

Gnomad EAS exome AF: 0.849

Gnomad FIN exome AF: 0.599

Gnomad NFE exome AF: 0.744

Gnomad OTH exome AF: 0.771

GnomAD4 exome AF: 0.751 AC: 399255 AN: 531640 Hom.: 150941 Cov.: 0 AF XY: 0.752 AC XY: 216810 AN XY: 288436

African (AFR) AF: 0.831 AC: 12827 AN: 15432

American (AMR) AF: 0.822 AC: 27983 AN: 34056

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 16552 AN: 19580

East Asian (EAS) AF: 0.777 AC: 24004 AN: 30894

South Asian (SAS) AF: 0.757 AC: 46753 AN: 61746

European-Finnish (FIN) AF: 0.617 AC: 19187 AN: 31120

Middle Eastern (MID) AF: 0.782 AC: 3124 AN: 3994

European-Non Finnish (NFE) AF: 0.741 AC: 226367 AN: 305334

Other (OTH) AF: 0.762 AC: 22458 AN: 29484

GnomAD4 genome AF: 0.763 AC: 116132 AN: 152120 Hom.: 44694 Cov.: 33 AF XY: 0.758 AC XY: 56369 AN XY: 74362

African (AFR) AF: 0.824 AC: 34178 AN: 41498

American (AMR) AF: 0.810 AC: 12386 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 2943 AN: 3468

East Asian (EAS) AF: 0.822 AC: 4248 AN: 5168

South Asian (SAS) AF: 0.742 AC: 3578 AN: 4824

European-Finnish (FIN) AF: 0.588 AC: 6218 AN: 10574

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.736 AC: 50040 AN: 67982

Other (OTH) AF: 0.789 AC: 1667 AN: 2114

Alfa AF: 0.759 Hom.: 165358

Bravo AF: 0.786

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.7
DANN	Benign	0.79
PhyloP100		-0.46
PromoterAI		0.052	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2239528; hg19: chr6-31510105;